title: Elucidating the role of interleukin-17F in cutaneous T-cell lymphoma.
abstract: Inappropriately regulated expression of interleukin (IL)-17A is associated with the development of inflammatory diseases and cancer. However, little is known about the role of other IL-17 family members in carcinogenesis. Here, we show that a set of malignant T-cell lines established from patients with cutaneous T-cell lymphoma (CTCL) spontaneously secrete IL-17F and that inhibitors of Janus kinases and Signal transducer and activator of transcription 3 are able to block that secretion. Other malignant T-cell lines produce IL-17A but not IL-17F. Upon activation, however, some of the malignant T-cell lines are able to coexpress IL-17A and IL-17F, leading to formation of IL-17A/F heterodimers. Clinically, we demonstrate that IL-17F messenger RNA expression is significantly increased in CTCL skin lesions compared with healthy donors and patients with chronic dermatitis. IL-17A expression is also increased and a significant number of patients express high levels of both IL-17A and IL-17F. Concomitantly, we observed that the expression of the IL-17 receptor is significantly increased in CTCL skin lesions compared with control subjects. Importantly, analysis of a historic cohort of 60 CTCL patients indicates that IL-17F expression is associated with progressive disease. These findings implicate IL-17F in the pathogenesis of CTCL and suggest that IL-17 cytokines and their receptors may serve as therapeutic targets.
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3c, Copenhagen, Denmark.
authors.forename: Thorbjørn
authors.initials: T
authors.lastname: Krejsgaard
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Litvinov
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Lixin
authors.initials: L
authors.lastname: Xia
authors.forename: Andreas
authors.initials: A
authors.lastname: Willerslev-Olsen
authors.forename: Sergei B
authors.initials: SB
authors.lastname: Koralov
authors.forename: Katharina L
authors.initials: KL
authors.lastname: Kopp
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Bonefeld
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhou
authors.forename: Denis
authors.initials: D
authors.lastname: Sasseville
authors.forename: Niels
authors.initials: N
authors.lastname: Odum
mesh_terms: D001706:Biopsy; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D019169:Jurkat Cells; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism*; D008297:Male; D009182:Mycosis Fungoides / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012867:Skin / Q000473:pathology
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053612:Janus Kinases